Combinatorial reporter-based approach using two invertebrate model organisms to identify adverse outcome pathways in developmental and reproductive toxicity
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Adverse Outcome Pathway
Reproductive toxicity
Developmental toxicity
A growing number of environmental contaminants have been proved to have reproductive toxicity to males and females. However, the unclear toxicological mechanism of reproductive toxicants limits the development of virtual screening methods. By consolidating androgen (AR)-/estrogen receptors (ERs)-mediated adverse outcome pathways (AOPs) with more than 8000 chemical substances, we uncovered relationships between chemical features, a series of pathway-related effects, and reproductive apical outcomes─changes in sex organ weights. An AOP-based computational model named RepTox was developed and evaluated to predict and characterize chemicals' reproductive toxicity for males and females. Results showed that RepTox has three outstanding advantages. (I) Compared with the traditional models (37 and 81% accuracy, respectively), AOP significantly improved the predictive robustness of RepTox (96.3% accuracy). (II) Compared with the application domain (AD) of models based on small in vivo datasets, AOP expanded the ADs of RepTox by 1.65-fold for male and 3.77-fold for female, respectively. (III) RepTox implied that hydrophobicity, cyclopentanol substructure, and several topological indices (e.g., hydrogen-bond acceptors) were important, unbiased features associated with reproductive toxicants. Finally, RepTox was applied to the inventory of existing chemical substances of China and identified 2100 and 7281 potential toxicants to the male and female reproductive systems, respectively.
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Anogenital distance
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Reproductive toxicity
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Adverse Outcome Pathway
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Dibutyl phthalate (DBP) has been found as a ubiquitous environmental pollutant with reproductive and developmental toxicity. The characteristics of reproductive and developmental toxicity of DBP, the mechanisms of the toxicity and effects on human health were reviewed in this paper according to the toxic effects on pregnant animals exposed to DBP, which might provide reference for the further study on toxicity of DBP and preventive measures.
Dibutyl phthalate
Developmental toxicity
Reproductive toxicity
Environmental toxicology
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Adverse Outcome Pathway
Reproductive toxicity
Environmental toxicology
Reproductive system
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Acrylamide(AA) is primarily generated in starchy food which heated up to 120 ℃. Researches showed that AA had reproductive toxicity, developmental toxicity, neurotoxicity and genetic toxicity to the body. Especially, the reproductive and developmental toxicity of AA attracted a great of attentions gradually. In the research of reproductive toxicity and developmental toxicity of AA, any indexes reflected reproductive system damage could be used as biomarkers of AA reproductive toxicity. As the same, any indexes reflected developmental system damage could also be used as biomarkers of AA developmental toxicity. As more and more biomarkers have been determined, they will play an important role in the risk assessment. Therefore, the evaluation of biomarker has very important significance in comprehensive research of AA reproductive and developmental toxicity. This paper reviewed the biomarker of reproductive and developmental toxicity of AA, and described them from various perspectives.
Reproductive toxicity
Developmental toxicity
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